Brief sleep disruption alters synaptic structures among hippocampal and neocortical somatostatin-expressing interneurons

Brief sleep loss can disrupt cognition, including information processing in neocortex and hippocampus. Recent studies have identified alterations in synaptic structures of principal neurons within these circuits ^1–3 . However, while in vivo recording and bioinformatic data suggest that inhibitory interneurons are more strongly affected by sleep loss ^4–9 , it is unclear how sleep and sleep deprivation affect interneurons’ synapses. Recent data suggest that activity among hippocampal somatostatin-expressing (SST+) interneurons is selectively increased by experimental sleep disruption ⁸ . We used Brainbow 3.0 ¹⁰ to label SST+ interneurons in the dorsal hippocampus, prefrontal cortex, and visual cortex of SST-CRE transgenic mice, then compared synaptic structures in labeled neurons after a 6-h period of ad lib sleep, or gentle handling sleep deprivation (SD) starting at lights on. We find that dendritic spine density among SST+ interneurons in both hippocampus and neocortex was altered in a subregion-specific manner, with increased overall and thin spine density in CA1, decreased mushroom spine density in CA3, and decreased overall and stubby spine density in V1 after SD. Spine size also changed significantly after SD, with dramatic increases in spine volume and surface area in CA3, and small but significant decreases in CA1, PFC and V1. Together, our data suggest that the synaptic connectivity of SST+ interneurons is significantly altered, in a brain region-specific manner, by a few hours of sleep loss. Further, they suggest that sleep loss can disrupt cognition by altering the balance of excitation and inhibition in hippocampal and neocortical networks.